Title :

Native glycosylation and binding of the antidepressant paroxetine in a low-resolution crystal structure of human myeloperoxidase

Author(s) :

Krawczyk, Lucas [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF]
Semwal, Shubham [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Soubhye, Jalal [Auteur]
Faculté de Pharmacie [Bruxelles] [ULB]
Lemri Ouadriri, Salma [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Prévost, Martin [Auteur]
Faculté des Sciences [Bruxelles] [ULB]
Van Antwerpen, Pierre [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Roos, Goedele [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Bouckaert, Julie [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576

Journal title :

Acta Crystallographica Section D Structural Biology

Volume number :

D78

Pages :

1099-1109

Publisher :

International Union of Crystallography (IUCr)

Publication date :

2022-08-09

ISSN :

2059-7983

English keyword(s) :

human myeloperoxidase
glycosylation
N-glycan refinement
thiocyanate
paroxetine

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Human myeloperoxidase (MPO) utilizes hydrogen peroxide to oxidize organic compounds and as such plays an essential role in cell-component synthesis, in metabolic and elimination pathways, and in the front-line defence ...
Show more >Human myeloperoxidase (MPO) utilizes hydrogen peroxide to oxidize organic compounds and as such plays an essential role in cell-component synthesis, in metabolic and elimination pathways, and in the front-line defence against pathogens. Moreover, MPO is increasingly being reported to play a role in inflammation. The enzymatic activity of MPO has also been shown to depend on its glycosylation. Mammalian MPO crystal structures deposited in the Protein Data Bank (PDB) present only a partial identification of their glycosylation. Here, a newly obtained crystal structure of MPO containing four disulfide-linked dimers and showing an elaborate collection of glycans is reported. These are compared with the glycans identified in proteomics studies and from 18 human MPO structures available in the PDB. The crystal structure also contains bound paroxetine, a blocker of serotonin reuptake that has previously been identified as an irreversible inhibitor of MPO, in the presence of thiocyanate, a physiological substrate of MPO.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Université de Lille
CNRS

Collections :

• Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576

Research team(s) :

Computational Molecular Systems Biology

Submission date :

2022-09-20T14:26:11Z
2022-09-21T13:39:55Z
2022-10-19T12:46:55Z